1. Field of the Invention
The present invention relates to a chondroitin sulfate synthesis promoter, and to a treatment agent for articular disease and discopathy employing the promoter.
2. Background Art
Cartilage contains a macromolecular substance, called aggrecan, which is predominantly formed of chondroitin sulfate proteoglycan. Aggrecan is a type of proteoglycan in which a polysaccharide sulfate is covalently bound to a core protein, and is known to play an important role in organisms. In cartilage, aggrecan, having a hyaluronic acid-binding domain in a core protein portion, forms a macromolecular complex with a link protein and hyaluronic acid. Aggrecan, having 100 or more chondroitin sulfate chains bound to a core protein portion thereof, retains a large number of water molecules. Thus, aggrecan is present in cartilage in the form of highly hydrated gel and is believed to play important roles such as absorbing shock and reducing friction (lubrication).
Meanwhile, several glycosyltransferases have recently been reported to be involved in synthesis of chondroitin sulfate chains: chondroitin synthase-1 (CSS-1, J. Biol. Chem., October 2001; 276: 38721-38726), chondroitin synthase-2 (CSS-2, J. Biol. Chem., August 2003; 278: 30235-30247, WO 03/102194), chondroitin synthase-3 (CSS-3, J. Biol. Chem., October 2003; 278: 39711-39725, WO 03/102193), chondroitin sulfate glucuronyltransferase (CSGlcAT, J. Biol. Chem., October 2002; 277: No. 41: 38179-38188), chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1, J. Biol. Chem., March 2002; 277: No. 11: 8841-8846), and chondroitin sulfate N-acetylgalactosaminyltransferase-2 (CSGalNAcT-2, J. Biol. Chem., January 2003; 278: 3063-3071, Japanese Patent Application Laid-Open (kokai) No. 2003-289883).
Although general functions of these enzymes are already known, the roles of these enzymes in organisms have not yet been elucidated. In addition, an enzyme involved in biosynthesis of chondroitin sulfate (a part of aggrecan biosynthesis) has not been identified. Therefore, whether or not these enzymes increase the amount of chondroitin sulfate in organisms remains unknown.